This research program is designed to elucidate the molecular mechanisms involved in the transmembrane communication between an extracellular regulating agent and the cell cytoplasm. The research program focuses on the system of cholera toxin (choleragen) and its separate subunits, interacting with its receptor in various model and natural membranes. The effects of choleragen and its binding subunit (choleragenoid) on bilayer permeability will be studied. The thermodynamics of the interactions of the toxin receptor (ganglioside GM1) with various lipid bilayers are being studied, along with the accessible thermal states of the toxin protein and its subunits. Studies of the interactions of the toxin with erythrocytes similar to those using liposomes will be undertaken in order to correlate the model membrane results with natural plasma membranes. A differential scanning calorimeter with variable sample pressure is being assembled as the major research technique used in this program. There are definite similarities between the actions of choleragen and other agents including some hormones, so that the results of this research will make contributions to the understanding of a broad class of receptor membrane interactions.